Field of Endeavor
The present invention relates to systems and methods for generating a direct electric current transcutaneously. More particularly, the invention relates to a neural stimulation device for generating a constant, direct current at a supraorbital location to relieve headaches and other ailments.
Background Information
The roots of migraine attacks are believed by some clinicians and researchers to be self-propagating waves of cerebral neuronal firing, known as spreading depolarizations. Worldwide, primary headache disorders are the fifth leading cause of disability for women. The annual prevalence of migraine in the United States is 18% for adult women and the lifetime prevalence of migraine for women is estimated to be 26%.
A variety of different nerves may contribute to migraines or similar ailments. FIGS. 1 and 2 show many of the nerves of the face and scalp of a human head 10. The supraorbital nerve 12, the supratrochlear nerve 14, infratrochlear nerve 16, the external nasal nerve 18, and the lacrimal nerve 20 are located around and above the eyes. The zygomatico-temporal nerve 22, the infraorbital nerve 24 and the zygomaticofacial nerve 26 are generally located on the cheek and side of the face up to the temple. The auriculotemporal nerve 28, the buccal nerve 30, the mental nerve 32 and the great auricular nerve 34 are located along the chin and extending to the ear. The greater occipital nerve 36 and lesser occipital nerve 38 are located near the rear of the head.
Devices have been developed to treat or prevent migraine headaches, pain, and other neurological disorders using a number of approaches. One approach using implanted electrodes (invasive devices) has been used with neurostimulation devices that deliver pulses of electrical current directly to targeted nerves. There are numerous reports using neurostimulation of the occipital nerves, supraorbital, and/or infraorbital nerves using implanted electrodes (especially located at the back of the head above the neck) for treatment of migraine headaches and craniofacial pain. However, a significant number of patients suffer side effects from the implanted electrodes. Many patients treated with implanted electrodes also suffer from lack of efficacy of these devices. Either the side effects or lack of efficacy often result in the removal or replacement of the electrodes. In one report 5 of 22 patients (22.7%) with a device with electrodes implanted to treat craniofacial pain had the device removed with a mean duration of follow-up of 35 months. The reasons for removal of the device were: two patients (9.1%) had the device removed because of pain improvement over time, two patients (9.1%) had the device removed due to loss of effectiveness, and one patient (4.6%) had the device removed due to late infection. The remainder of the patients enjoyed either complete (15 patients, 68.2%) or partial (two patients, 9.1%) pain relief. Three patients (13.6%) underwent repeated operations due to lead erosion, infection or electrode migration.
There are reports of the neurostimulation of the occipital nerves, supraorbital and/or infraorbital nerves with implanted electrodes (posterior head superior to the neck) for treatment of migraine headaches and craniofacial pain. In a randomized, controlled multicenter study of patients diagnosed with chronic migraine, patients were implanted with a neurostimulation device near the occipital nerves and then randomized 2:1. The primary endpoint of this study was the percentage of responders (defined as patients that achieved a ≧50% reduction in mean daily visual analog scale scores) in each group at 12 weeks. The authors reported that there was no significant difference in the percentage of responders in patients with the Active device when compared with the Control device (95% lower confidence boundary of −0.06; p=0.55). However, when the results of the sham-treated patients were compared with the Active device treated patients, there were statistically significant reductions in secondary endpoints: number of headache days (Active device 6.1 decreased headache days from a baseline of 22.4 headache days versus Control device decreased 3.0 headache days 3.0 from a baseline of 20.1 headache days; p=0.008). Also, decreased by the Active treatment versus Control were migraine-related disability (p=0.001) and direct reports of pain relief (p=0.001). The most common adverse event reported in the study was persistent implant site pain.
In U.S. Pat. No. 6,735,475 to Whitehurst et al. discloses a fully implantable miniature neurostimulator for stimulation as a therapy for headache and/or facial pain. U.S. Pat. No. 8,577,466 to Mashiach et al. describes a device configured for implantation into a body of a subject that may include an antenna configured to receive a signal. The implantable device may also include at least one pair of modulation electrodes configured to be implanted into the body of the subject in the vicinity of at least one nerve to be modulated. In this device at least one pair of modulation electrodes is configured to receive an applied electric signal. In response to the signal received by the antenna an electrical field modulates at least one nerve from a position where at least one pair of modulation electrodes does not contact at least one nerve.
Sphenopalatine interventions (ablations or nerve stimulation) have been used for over 100 years to treat migraine headaches. Another implantable device is a sphenopalatine ganglion neurostimulator that is implanted through an oral incision and placed along the maxilla. This device can apply on-demand sphenopalatine ganglion stimulation for the treatment of severe primary headache. However, invasive neurostimulator devices to ameliorate migraines remain unpopular with most migraine patients, largely due to lack of efficacy and post-surgical complications.
In one example, two patients had the devices removed because of pain improvement over time; in three patients the devices were removed due to loss of effectiveness (two cases) or late infection (one). The rest are enjoying either complete (15 patients) or partial (two patients) pain relief. Three patients underwent repeated operations due to lead erosion, infection or migration. Patients were implanted with a neurostimulation device near the occipital nerves and randomized 2:1 into a randomized, controlled multicenter study of patients diagnosed with chronic migraine. The primary endpoint was a difference in the percentage of responders (defined as patients that achieved a ≧50% reduction in mean daily visual analog scale scores) in each group at 12 weeks. They observed no significant difference in the percentage of responders in the Active compared with the Control group (95% lower confidence bound (LCB) of −0.06; p=0.55). However, there was a significant reduction in the number of headache days (Active Group median reduction of 6.1 days from a baseline of 22.4 days versus Control Group median reduction of 3.0 days from a baseline of 20.1 days; p=0.008). Also reported were migraine-related disability decreased (p=0.001) and direct reports of pain relief decreased (p=0.001). The most common adverse event reported in the study was persistent implant site pain.
Application of modulating electric signals via implanted electrodes attached directly to the nerves to be stimulated—either to one or both of a patient's trigeminal and glossopharyngeal nerves may treat, control or prevent of medical, psychiatric or neurological disorders; examples include: voluntary and involuntary disorders; migraine; epileptic seizure; motor disorders; Parkinson's disease; cerebral palsy; spasticity; chronic nervous illnesses and involuntary movement; pancreatic endocrine disorders including diabetes and hypoglycemia; dementia including cortical, subcortical, multi-infarct, Alzheimer's disease; Pick's disease; sleep disorders including central sleep apnea, insomnia and hypersomnia; eating disorders including anorexia nervosa, bulimia and compulsive overeating; and neuropsychiatric disorders including schizophrenia, depression and borderline personality disorder (See U.S. Pat. No. 5,540,734).
U.S. Pat. No. 6,954,668 describes an apparatus for intra-oral stimulation of the trigeminal nerve includes an energy source that imparts energy to a tooth to stimulate the trigeminal nerve and an attachment portion to secure the energy source in a mouth in proximity to the tooth. This stimulation has been experimentally shown to induce and/or enhance relaxation and/or sleep.
Invasive stimulation of the occipital nerve has been used to reduce migraine headaches in migraine patients. Complete diary data were available for 66 of the 75 patients. Responders achieved at least a 50% reduction in the number of headache days per month or a three-point or greater reduction in average overall pain intensity compared with baseline. The three-month responder rates were 39% for AS, 6% for PS and 0% for MM. No unanticipated adverse device events occurred.
The effect of pulsed electromagnetic fields on migraine activity has been evaluated in a double-blind, placebo-controlled study of 42 subjects (34 women and 8 men), who were selected to meet the International Headache Society's migraine criteria. Subjects kept a one month, pretreatment, baseline log of headache activity prior to being randomized to having either actual or placebo pulsing electromagnetic fields applied to their inner thighs for one hour per day, five days per week for two weeks. After exposure, all subjects kept the log for at least one month of follow-up. During the first month of follow-up, 73% of subjects receiving actual exposure reported decreased headaches (45% “good decrease,” 14% “excellent decrease” in headache activity) compared to half of those receiving the placebo (15% worse, 20% good, 0% excellent decrease in headache activity). Ten of the 22 subjects who had actual exposure received two additional weeks of actual exposure after their initial one month follow-up. All showed decreased headache activity (50% good, 38% excellent). Thirteen subjects from the actual exposure group elected not to receive additional exposure. Twelve of them showed decreased headache activity by the second month (29% good, 43% excellent decrease in headache activity). Eight of the subjects in the placebo group elected to receive two weeks of actual exposure after the initial one month follow-up with 75% showing decreased headache activity (38% good and 38% excellent decrease in headache activity). In conclusion, exposure of the inner thighs to pulsing electromagnetic fields for at least three weeks appears to be an effective, short-term intervention for migraine, but not tension headaches.
A non-invasive transcranial magnetic stimulator device for headache (Neuralieve) has been approved for marketing by the US Food and Drug Administration. This device described by Fischell et al. delivers brief duration, rapidly alternating, or pulsed, magnetic fields that are externally directed at spatially discrete regions of the brain to induce electrical currents for the treatment of headache.
U.S. Pat. No. 7,494,458 to Fischell et al. discloses an electromagnetic device that employs is a self-contained, battery operated, readily portable and easy-to-operate head-mounted magnetic depolarizer to generate a transient or time-varying high-intensity magnetic field. The magnetic field is directed into and around the user's head or neck to depolarize the neurons of the brain and/or the trigeminal nerve creating neuronal depolarization and terminate migraine or other types of headaches.
U.S. Pat. No. 6,402,678 to Fischell et al. discloses a device and method for treatment of migraine headaches using an intense magnetic field onto a region of the brain. An electrical current can be generated in the cerebral cortex that can depolarize a band of excited brain neurons that are a precursor to a migraine headache. The device can be positioned using headgear such as a bicycle helmet to direct the magnetic field at the correct part of the brain.
U.S. Pat. No. 8,262,556 to Fischell et al. discloses a means and methods for treatment of migraines and other disorders by application of intense magnetic pulses. They report stopping or decreasing the severity of migraine headaches using this magnetic pulser system.
The efficacy and safety of the Neuralieve device was tested in a randomized, double-blind, parallel-group, two-phase, sham-controlled study at 18 centers. A total of 267 adult patients (18-68 years of age) were enrolled in part 1 of the study. All individuals met the international criteria for migraine with aura, with visual aura preceding at least 30% of migraines followed by moderate or severe headache in more than 90% of those attacks. Sixty-six patients dropped out during part 1 of the study. For part 2 of the study, 201 patients were randomly allocated to either sham stimulation (n=99) or transcranial magnetic stimulation (n=102). Participants were instructed to treat up to three attacks over 3 months while experiencing aura. The primary outcome was pain-free response 2 hours after the first attack, and co-primary outcomes were non-inferiority at 2 hours for nausea, photophobia, and phonophobia.
Thirty-seven (37) patients failed to treat a migraine attack and were excluded from outcome analyses; 164 patients treated at least one attack with transcranial magnetic stimulation (n=82) or sham stimulation (n=82; modified intention-to-treat analysis set). Pain-free response rates after 2 hours were significantly higher with transcranial magnetic stimulation (32/82 [39%]) than with sham stimulation (18/82 [22%]), for a therapeutic gain of 17% (95% CI 3-31%; p=0·0179). Sustained pain-free response rates significantly favored transmagnetic stimulation at 24 hours and 48 hours post-treatment. Non-inferiority was shown for nausea, photophobia and phonophobia. No device-related serious adverse events were recorded, and the incidence and severity of adverse events were similar between transmagnetic stimulation and sham groups.
U.S. Pat. No. 8,428,734 to Rigaux et al. discloses a non-invasive transcutaneous electrical nerve stimulation (TENS) device (Cefaly device) has an electrical circuit that includes a programmable signal generator that produces pulses of electricity of between 150 and 450 microseconds duration with a maximum increase in intensity of 0 to 20 milliamperes at a rate of less than or equal to 40 microamperes per second and with a step up in intensity not exceeding 50 microamperes to stimulate the afferent paths of the supratrochlear and supraorbital nerves of the ophthalmic branch of the trigeminal nerve to prevent tension headaches or migraines.
However, the application of electrodes and significant electrical current to the forehead may produce extreme pain. The level of current applied, and thus tissue penetration, by this device is limited by the local pain and irritation associated with increased electrical current. Electrical stimulation devices are therefore of generally limited efficacy and acceptability for treatment of migraine and other primary headaches.
A double-blinded, randomized, sham-controlled trial testing the Cefaly device for control of migraine headaches was conducted at five Belgian tertiary headache clinics. Following a one month run-in, those patients with at least two migraine attacks per month were randomized at a 1:1 ratio to Cefaly or sham treatment. The Cefaly or sham treatment was applied daily for 20 minutes for a period of three months. The primary outcome measures for this study were the change in migraine days per month and the rate of 50% or greater responders. Sixty-seven patients were randomized and included in the intention-to-treat analysis. Between the run-in and third month of treatment, the mean number of migraine days decreased significantly in the Cefaly treatment group (6.94 versus 4.88; p=0.023), but not in the sham group (6.54 versus 6.22; p=0.608). The 50% or responder rate was significantly greater (p=0.023) in the Cefaly treatment group (38.1%) than in the sham group (12.1%). The number of monthly migraine attacks (p=0.044), the monthly headache days (p=0.041), and the monthly acute antimigraine drug intake (p=0.007) were also significantly reduced in the Cefaly treatment group but not in the sham group. There were no adverse events reported in either the Cefaly or the sham treatment groups.
U.S. Pat. No. 7,988,613 to Becker discloses an apparatus for generating frequencies of pulsed direct current signals that are related to sleep and alert states. This device is comprised of a circuit configured to produce a pulsed direct current signal having a frequency wherein the frequency falls within a range of brain wave frequencies. The device is capable of producing corresponding segments of pulsed direct current including a delta segment, a theta segment, an alpha segment and a beta segment. Each of the delta, theta, alpha and beta segments to a respective subrange of the brain wave frequencies. A frequency controller, coupled to the circuit, is configured to change the frequency of the pulsed direct current signal from a first frequency to a second frequency, wherein the second frequency is within a second one of the plurality of segments, and wherein the first frequency is a non-zero frequency outside of the second one of the plurality of segments. An inductor coil, coupled to the output of the circuit, is configured to generate a magnetic field from the pulsed direct current signal.
U.S. Pat. Nos. 8,676,324 and 8,676,330 to Simon et al. disclose non-invasive transcutaneous electrical nerve stimulation devices and magnetic stimulation devices. Methods of treating medical disorders using the energy delivered by these devices including migraine and other primary headaches such as cluster headaches, including nasal or paranasal sinus symptoms that resemble an immune-mediated response (“sinus” headaches). These disclosed methods may also be used to treat other disorders that may be co-morbid with migraine headaches, such as anxiety disorders. The disclosed methods may be used to stimulate one or both of the patient's vagus nerves or parts of the sympathetic nervous system and/or the adrenal glands.
In view of the foregoing, there is a need to provide an effective, painless, inexpensive apparatus for treating headaches, aura and other ailments for the large population of afflicted individuals who do not desire or could otherwise not afford pharmacologic or electromagnetic treatments.
It is also desirable to provide an apparatus and method for treating headaches, aura and similar pain using an effective and non-invasive procedure.